A critical area of Long COVID research is determining how and why, of the roughly one billion people around the world who have been infected with coronavirus, a large portion will go on to suffer debilitating disease effects for months or even years. As scientists grapple with the complexities of Long COVID, some patterns have been emerging.*

Two Groups of Long COVID Patients

Akiko Iwasaki, Ph.D., a scientist and Yale University professor of immunobiology, says there appear to be two primary groups of people who go on to experience lingering symptoms of SARS-CoV-2 infection:

• People who had mild COVID-19, or were asymptomatic, as is most long COVID patients
• People who survive severe COVID-19, often involving hospitalization and intensive care

Going deeper, research points to two sex-related subtypes based on immune response to the virus:

• Women aged 20-60 years tend to have mild or asymptomatic illness.
• Older men with risk factors tend to have severe COVID-19.

A Matter of X and Y?

Erica Ollmann Saphire, Ph.D., President and CEO of the La Jolla Institute for Immunology, says it’s well-established that men and women exhibit different immune responses to many diseases. Adult females typically react more strongly to pathogens than males, disposing of them more rapidly, which makes them more vulnerable to autoimmune disorders.

According to Ollmann Saphire, this difference often stems from the action of genes–found on X or Y chromosomes–that either trigger or suppress the immune system. Because men are XY and women XX, women have twice the capacity of the X chromosome that can alter immune responses between the sexes.

She says this difference could explain “man flu,” where men actually get sicker from influenza than women. On the other hand, the gene associated with the autoimmune disorder lupus is found on the X chromosome, and we know that women are 10 times more likely to develop lupus than men.

Implications for Long COVID

“The observation with Covid is that males have more severe initial disease, whereas females are more likely to have prolonged disease,” said Ollmann Saphire. 

These gender-related differences offer a strong clue that could lead to the molecular cause of Long COVID and an eventual solution. “If we can understand what was the gene, what was the cell, we can find a solution.”

*Gale, J. (2022, April 21). Sex-Linked Differences in Covid Immune Response. Bloomberg. https://www.bloomberg.com/news/newsletters/2022-04-21/pandemic-latest-read-the-bloomberg-coronavirug-newsletter